Bristol-Pfizer Team on Alert as FDA Reviews Stroke-Prevention Drug From Rivals J&J and Bayer

In 2007, New York-based pharmaceutical giants Bristol-Myers Squibb (NYS: BMY) and Pfizer (NYS: PFE) formed a deal to develop Bristol's anti-clotting drug, apixaban (Eliquis). The partnership hit a high point on August 28, when the two companies announced positive results from a Phase 3 trial of the drug in patients with the heart-rhythm disorder atrial fibrillation -- data that will be key when they apply for FDA approval later this year.

But an event happening today at the FDA may be equally important to the future of apixaban. An advisory panel to the agency is meeting to discuss rivaroxaban (Xarelto), an anti-clotting drug that Johnson & Johnson (NYS: JNJ) and Bayer developed. They are hoping to win FDA approval in November to market rivaroxaban to patients with atrial fibrillation.

Both apixaban and rivaroxaban are in a new class of drugs known as "factor Xa inhibitors." Factor X is one of the enzymes that promotes clotting, so inhibiting it helps to prevent strokes or embolisms -- common risks in patients with atrial fibrillation. The two drugs were developed with the goal of offering alternatives to warfarin, a 60-year-old anti-clotting product that can cause dangerous side effects such as severe bleeding.

In an interview yesterday, Jack Lawrence, a VP at Bristol and development lead for apixaban, said he was looking forward to the FDA's discussion on J&J and Bayer's competing drug. "There are always learnings in how other sponsors approach the FDA's questions," he says. "It will be a fascinating discussion. And sometimes it helps not to be the first to go through that process."

The FDA review is shaping up to be a painful process for J&J and Bayer. On September 6, the FDA posted a nasty review of rivaroxaban on the Web, the upshot of which was to suggest the companies be forced to perform another clinical trial before they get the drug approved in atrial fibrillation. The data, says the review, suggests that patients taking the drug "might be at greater risk of harm from stroke and/or bleeding than if they were treated with warfarin used skillfully." It goes on to say that the companies should have to produce additional data proving safety and efficacy.

The Bristol-Pfizer team is hopeful that apixaban will get a more welcome reception from the FDA. In the trial announced in August, apixaban reduced the risk of stroke or embolism by 21 percent, and it cut the risk of major bleeding by 31 percent, when compared to warfarin. Mortality dropped by 11 percent. "When we began trials six years ago, we were hoping to develop a drug that was as effective and more convenient than warfarin, but these results show we did much more than that," says Christopher Granger, professor of medicine at the Duke Clinical Research Institute, and the lead investigator for the trial. In particular, he says, the reduction in bleeding risk "was spectacular."

The convenience advantage should come from the amount of follow-up patients require, Granger adds. People who are prescribed warfarin often have to see their doctors once a month or more to get the clotting ability of their blood measured, at which point patients' doses might have to be tweaked. Apixaban shouldn't require that level of routine monitoring, Granger says.

Bristol's scientists discovered apixaban and completed the early phases of development before deciding to take on a partner in the mid-2000s. The company's executive knew the Phase 3 program would have to be enormous, Lawrence says. (The most recent trial included 18,000 patients.) "We realized having a partner would be desirable, given the size and cost of the program, as well as our desire for the drug to have a broad presence around the world," he says. Bristol put out a call to other pharma companies, inviting partnership proposals.

Pfizer answered the call, and ended up being the ideal partner, Lawrence says. "Pfizer brings a very science-driven approach to development, and a rigorous approach to marketing," he says. He adds that Pfizer's marketing presence around the world will help Bristol fill gaps in regions where it is not as well-resourced.

Bristol has not estimated the market opportunity for apixaban, beyond citing estimates that atrial fibrillation affects 5 million Americans and 6 million Europeans. There are other competitors, including dabigatran (Pradaxa), an anti-clotting drug from Boehringer Ingelheim that was approved in 2010 for preventing stroke in atrial fibrillation patients.

Still, some analysts looked at the recent data on apixaban and predicted Bristol and Pfizer would have a major hit on their hands -- even if they're third to market. In an August 29 report on Bristol, Leerink Swann analyst Seamus Fernandez predicted that in 2017, apixaban will bring in sales of $2.7 billion in the U.S. The Boehringer and J&J/Bayer products will bring in $1 billion and $1.6 billion respectively, he guesses. In his report, Fernandez called apixaban's safety and tolerability profile "superb." He added that both Bristol and Pfizer "bring unparalleled marketing prowess in cardiovascular disease," courtesy of Bristol's blood-thinner clopidogrel (Plavix) and Pfizer's cholesterol blockbuster atorvastatin (Lipitor).

For now, Bristol is concentrating on putting together the best package it can for the FDA review of apixaban -- a process that can only be helped by observing how rivals J&J and Bayer handle the tough questions they're getting from the agency today. "It's nice to be first," Lawrence says, "but if you're attentive as the number-three player, there's a chance you'll come out ahead."